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Originally published In Press as doi:10.1074/jbc.M413466200 on February 14, 2005

J. Biol. Chem., Vol. 280, Issue 18, 18171-18178, May 6, 2005
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A Conserved Mediator Hinge Revealed in the Structure of the MED7·MED21 (Med7·Srb7) Heterodimer*

Sonja Baumli, Sabine Hoeppner, and Patrick Cramer{ddagger}

From the Gene Center, University of Munich (Ludwig-Maximilians-Universität), Department of Chemistry and Biochemistry, Feodor-Lynen-Strasse 25, 81377 Munich, Germany

The Mediator of transcriptional regulation is the central coactivator that enables a response of RNA polymerase II (Pol II) to activators and repressors. We present the 3.0-Å crystal structure of a highly conserved part of the Mediator, the MED7·MED21 (Med7·Srb7) heterodimer. The structure is very extended, spanning one-third of the Mediator length and almost the diameter of Pol II. It shows a four-helix bundle domain and a coiled-coil protrusion connected by a flexible hinge. Four putative protein binding sites on the surface allow for assembly of the Mediator middle module and for binding of the conserved subunit MED6, which is shown to bridge to the Mediator head module. A flexible MED6 bridge and the MED7·MED21 hinge could account for changes in overall Mediator structure upon binding to Pol II or activators. Our results support the idea that transcription regulation involves conformational changes within the general machinery.


Received for publication, November 30, 2004 , and in revised form, January 18, 2005.

The atomic coordinates and structure factors (codes 1YKH and 1YKE) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/).

* This work is supported by the Deutsche Forschungsgemeinschaft, the Fonds der Chemischen Industrie, and the EMBO Young Investigator Programme. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

{ddagger} To whom correspondence should be addressed. Tel.: 49-89-2180-76951; Fax: 49-89-2180-76999; E-mail: cramer{at}LMB.uni-muenchen.de.


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